Physiological and biochemical studies of newly synthesized muscarinic acetylcholine receptors in embryonic chicken heart
Exposure of either chicken embryos in ovo or cultured embryonic chicken cardiac cells in vitro to the muscarinic agonist carbachol results in a 70-90% decrease in the number of muscarinic acetylcholine receptors (mAChR) expressed in cardiac cells. Block of agonist-receptor interactions in ovo with the antagonist atropine or removal of the agonist in vitro results in a gradual increase in mAChR number, reaching the control level in 14 hr. Measurements of physiological sensitivity of atria or cultured cells show that, even after the complete recovery of receptor number, the sensitivity to agonist is reduced. The sensitivity of the mAChR-mediated inhibition of adenylate cyclase is also decreased at this time. Newly synthesized mAChR which appear following affinity alkylation in cultured cells are also poorly coupled to the stimulation of /sup 86/Rb/sup +/ efflux, indicating that decreased physiological sensitivity is not due to an unknown effect of long-term agonist exposure on general cellular function, but rather reflects an intrinsic property of newly synthesized mAChR. This increase in sensitivity is also not blocked by cycloheximide. The increase in sensitivity of the mAChR-mediated responses is due neither to a lack of expression of newly synthesized mAChR on the surface nor to reduced agonist affinity of the mAChR. The diminished sensitivity and subsequent maturation observed in cells containing newly synthesized receptors is due either to a small change in mAChR, or to a change in an as-yet-undefined component of the mAChR transduction system; this alteration represents a novel locus for modulation of cholinergic signals in the heart.
- Research Organization:
- Washington Univ., Seattle (USA)
- OSTI ID:
- 5561461
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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HEART
PHYSIOLOGY
RECEPTORS
BIOCHEMISTRY
RUBIDIUM 86
MEMBRANE TRANSPORT
ACETYLCHOLINE
CHICKENS
EMBRYONIC CELLS
EMBRYOS
IN VITRO
ALKALI METAL ISOTOPES
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIRDS
BODY
CARDIOVASCULAR SYSTEM
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DRUGS
ESTERS
FOWL
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MEMBRANE PROTEINS
MINUTES LIVING RADIOISOTOPES
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
PROTEINS
QUATERNARY COMPOUNDS
RADIOISOTOPES
RUBIDIUM ISOTOPES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
551001 - Physiological Systems- Tracer Techniques